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BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

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BACKGROUND: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration. METHODS: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d6)-α- and dideuterium (d2)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d6-α- and d2-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18-20 h. As predicted, during vitamin C supplementation, the rates of plasma d6-α-tocopherol decline were significantly slower. CONCLUSIONS: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.

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Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 µg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.

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Antioxidant interactions of γ-terpinene with α-tocopherol mimic 2,2,5,7,8-pentamethyl-6-chromanol (PMHC) and caffeic acid phenethyl ester (CAPE), used as models, respectively, of mono- and poly-phenols were demonstrated by differential oximetry during the inhibited autoxidation of model substrates: stripped sunflower oil, squalene, and styrene. With all substrates, γ-terpinene acts synergistically regenerating the chain-breaking antioxidants PMHC and CAPE from their radicals, via the formation of hydroperoxyl radicals. The inhibition duration for mixtures PMHC/γ-terpinene and CAPE/γ-terpinene increased with γ-terpinene concentration, while rate constants for radical-trapping were unchanged by γ-terpinene, being 3.1 × 106 and 4.8 × 105 M-1s-1 for PMHC and CAPE in chlorobenzene (30 °C). Using 3,5-di-tert-butylcatechol and 3,5-di-tert-butyl-1,2-bezoquinone we demonstrate that γ-terpinene can reduce quinones to catechols enabling their antioxidant activity. The different synergy mechanism of γ-terpinene with mono- and poly-phenolic antioxidants is discussed and its relevance is proven in homogenous lipids using natural α-tocopherol and hydroxytyrosol as antioxidants, calling for further studies in heterogenous food products.

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A previously unreported dihydrochromone dimer, paecilin E (1), was isolated, together with eleven known compounds: ß-sitostenone, ergosta-4,6,8 (14), 22-tetraen-3-one, cyathisterone, byssochlamic acid, dehydromevalonic acid lactone, chevalone B, aszonalenin, dankasterone A (2), helvolic acid, secalonic acid A and fellutanine A, from the culture filtrate extract of the marine sponge-associated fungus Neosartorya fennelliae KUFA 0811. Nine previously reported metabolites, including a chromanol derivative (3), (3ß, 5α, 22E), 3,5-dihydroxyergosta-7,22-dien-6-one (4), byssochlamic acid, hopan-3ß,22-diol, chevalone C, sartorypyrone B, helvolic acid, lumichrome and the alkaloid harmane were isolated from the culture of the marine-sponge associated fungus Neosartorya tsunodae KUFC 9213. Paecilin E (1), dankasterone A (2), a chromanol derivative (3), (3ß, 5α, 22E)-3,5-dihydroxyergosta-7,22-dien-6-one (4), hopan-3ß,22-diol (5), lumichrome (6), and harmane (7) were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. While paecilin E (1) was active against S. aureus ATCC 29213 and E. faecalis ATCC 29212, dankastetrone A (2) was only effective against E. faecalis ATCC 29212 and the multidrug-resistant VRE E. faecalis A5/102. Both compounds neither inhibit biofilm mass production in any of the strains at the concentrations tested nor exhibit synergistic association with antibiotics.

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VECAR are novel bolaamphiphilic molecules consisting of two hydrophilic molecular groups, a carnosine derivative and a chromanol group, covalently linked by a hydrophobic alkyl spacer of varying length. Despite the potential for application in various biomedical applications VECAR properties, including their bulk properties, are still largely unknown. The early stage of the self-assembly process of VECAR molecules in water is studied using molecular dynamics simulations. The study reveals that the length of the hydrophobic spacer in VECAR affects the aggregation kinetics as well as the size, shape, density, and atomistic structure of the self-assembled aggregates. A mechanism based on cooperative interactions between water, the hydrophilic hydroxyl group, and the hydrophobic benzene ring of the chromanol head is proposed to explain the ordered packings of chromanols in the self-assembled aggregate structures at the aggregate-water interface.

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To evaluate the antibacterial activity of 12 ethanol extracts of Thai traditional herb against oral pathogens. The antibacterial activities were assessed by agar well diffusion, broth microdilution, and time-kill methods. Antibiofilm activity was investigated using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium-bromide (MTT) assay. High performance liquid chromatography (HPLC), thin layer chromatography (TLC) fingerprinting, and TLC-bioautography were used to determine the active antibacterial compounds. Piper betle showed the best antibacterial activities against all tested strains in the minimal inhibitory concentration and minimal bactericidal concentration, ranged from 1.04-5.21 mg/mL and 2.08-8.33 mg/mL, respectively. Killing ability depended on time and concentrations of the extract. P. betle extract acts as a potent antibiofilm agent with dual actions, preventing and eradicating the biofilm. The major constituent of P. betle extract was 4-chromanol, which responded for antibacteria and antibiofilm against oral pathogens. It suggests that the ethanol P. betle leaves extract may be used for preventing oral diseases.

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High levels of alpha-tocopherol, the usual vitamin E supplement, are reported to decrease bone mass in rodents; however, the effects of other vitamin E forms on the skeleton are unknown. To test the hypothesis that high intakes of various vitamin E forms or the vitamin E metabolite, carboxyethyl hydroxy chromanol, were detrimental to bone status, Sprague-Dawley rats (n = 6 per group, 11-week males) for 18 weeks consumed semipurified diets that contained adequate alpha-tocopherol, high alpha-tocopherol (500 mg/kg diet), or 50% Tocomin (250 mg mixed tocopherols and tocotrienols/kg diet). Vitamin E status was evaluated by measuring plasma, liver, and bone marrow vitamin E concentrations. Bone density, microarchitecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and cancellous bone volume fraction, trabecular number, thickness, and spacing), and cancellous bone formation were assessed in the tibia using dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry, respectively. In addition, serum osteocalcin was assessed as a global marker of bone turnover; gene expression in response to treatment was evaluated in the femur using targeted (osteogenesis related) gene profiling. No significant differences were detected between treatment groups for any of the bone endpoints measured. Vitamin E supplementation, either as alpha-tocopherol or mixed tocotrienols, while increasing vitamin E concentrations both in plasma and tissues, had no effect on the skeleton in rats.

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Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their specific growth media offers an alternative and simple preservation method to liquid nitrogen cryopreservation or commercial preservation fluids for short-term storage and transport. However, accumulation of cell damage during hypothermia may result in cell injury and death upon rewarming through the production of excess reactive oxygen species (ROS). Here, the ability of the cell culture medium additive SUL-109, a modified 6-chromanol, to protect ASC from hypothermia and rewarming damage is examined. SUL-109 conveys protective effects against cold-induced damage in ASC as is observed by preservation of cell viability, adhesion properties and growth potential. SUL-109 does not reduce the multilineage differentiation capacity of ASC. SUL-109 conveys its protection against hypothermic damage by the preservation of the mitochondrial membrane potential through the activation of mitochondrial membrane complexes I and IV, and increases maximal oxygen consumption in FCCP uncoupled mitochondria. Consequently, SUL-109 alleviates mitochondrial ROS production and preserves ATP production. In summary, here we describe the generation of a single molecule cell preservation agent that protects ASC from hypothermic damage associated with short-term cell preservation that does not affect the differentiation capacity of ASC.

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Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors. In particular, it was shown that melatonin was able to inhibit growth/viability and proliferation, to reduce the invasiveness and metastatic properties of human estrogen-sensitive breast adenocarcinoma MCF-7 cell line cultured in growth medium, with substantial impairments of epidermal growth factor (EGF) and Notch-1-mediated signaling. The purpose of this work was to evaluate on MCF-7 cells the possible effects of melatonin on the biophysical features known to have a role in proliferation and differentiation, by using the patch-clamp technique. Our results show that in cells cultured in growth as well as in differentiation medium melatonin caused a hyperpolarization of resting membrane potential paralleled by significant changes of the inward Ca(2+) currents (T- and L-type), outward delayed rectifier K(+) currents and cell capacitance. All these effects are involved in MCF-7 growth and differentiation. These findings strongly suggest that melatonin, acting as a modulator of different voltage-dependent ion channels, might be considered a new promising tool for specifically disrupting cell viability and differentiation pathways in tumour cells with possible beneficial effects on cancer therapy.

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Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic ß-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive ß-cells and GLP-1-positive L-cells. Administration of chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.

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The development of a convenient mathematical application for testing the antioxidant and pro-oxidant capacity is essential in order to investigate potential sources of new agents and processes. In this regard, authors use the standardized values of the area under the curve of a kinetic profile of a dose-response agent, as a way to bypass the complex process of analyzing the kinetic variations of agents. In general, linear approaches are used, but such patterns frequently lead to unreliable results and misinterpretations, making it extremely difficult to compare the results from different assays. In this work, we have demonstrated the non-linearity of the dose-response area under the curve assessment criteria by means of simulations. A simple non-linear dose-response model was developed to describe the accurate response. As a case study, experimental data of extracts of unroasted coffee beans from five different country-climate locations for the two most common coffee varieties (Robusta and Arabica) were obtained using the ß-carotene and crocin bleaching in vitro assays. Their antioxidant capacity was analyzed in detail and compared with commercial standards. The results show that the antioxidant capacity was greater than some of the commercial standards in terms of its maximum capacity, while when the analyses are based on rate parameters, the coffee extracts show between 6 and 40 times lower values than the standard antioxidants. In addition, to illustrate the advantages of using the standardized area units and the mathematical model developed, other more complex scenarios were recreated. We believe that the model application developed provides a simple alternative to summarize meaningful parameters that characterize the response, facilitates rigorous comparisons among the effects of different compounds and experimental approaches and helps to comprehend multi-variable scenarios.